In vitro and in vivo tumor suppressive activity induced by human telomerase transcriptase-targeting antisense oligonucleotides mediated by cationic liposomes.
The objective of this study was to investigate the in vitro and in vivo influence of cationic liposomes on the tumor suppressive effect of antisense telomerase oligodeoxynucleotides to human cervical adenocarcinoma cells (HeLa). Antisense oligodeoxynucleotides (ASODN) against the human telomerase transcriptase (hTERT) served as telomerase inhibitors. The cholesterol derivative, 3beta [N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), was synthesized, and cationic liposomes (CL) were prepared using DC-Chol and dioleoylphosphatidylethanolamine (DOPE). The in vitro IC50 of the CL-ASODN complex was 1.88 mumol/l, while the IC50 of the cells treated with free ASODNs or CL alone was 25.24 mumol/l and 55.18 mumol/l, respectively. The CL-ASODN complex inhibited HeLa cell growth for at least 120 h. In vivo, the CL-ASODN complex inhibited the tumor growth rate by 55.11%, which increased to 89.47% when CL-ASODN was combined with 5-fluorouracil treatment. ASODNs alone failed to induce tumor-suppressive activity, suggesting that CL prepared from DOPE and DC-Chol can significantly enhance the growth inhibitory effect of ASODN on tumor cells both in vitro and in vivo.
Han
Min
M
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Chen
Jin-Liang
JL
Hu
Ying
Y
He
Cai-Li
CL
Shuai
Wu-Ping
WP
Yu
Jian-Heng
JH
Chen
Hai-Liang
HL
Liang
Wen-Quan
WQ
Mayumi
Tadanori
T
Shinsaku
Nakagawa
N
Gao
Jian-Qing
JQ
D002412:Cations; D002470:Cell Survival / Q000235:genetics*; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D002412:Cations; D004337:Drug Carriers; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D019098:Telomerase